The morphogen gradients that underpin tissue patterning are often regulated by negative feedback in which the morphogen upregulates the expression of inhibitors that attenuate morphogen signalling. Jeong and McMahon now report that the hedgehog (Hh) antagonists patched 1 (Ptch1) and hedgehog-interacting protein 1 (Hhip1), both of which are upregulated by Hh signalling,synergistically regulate growth and patterning in the mouse neural tube (see ). Ptch1 induces the rapid endocytosis and degradation of sonic hedgehog (Shh), which controls patterning in the mammalian spinal cord; Hhip1 sequesters Shh at the cell surface. The researchers show that mouse embryos lacking both Ptch1and Hhip1 activities have severe neural tube patterning defects that are consistent with an increased magnitude and range of Hh signalling. This and other results indicate that, as in flies, Ptch1 helps to control Hh gradients through ligand-dependent antagonism. However, in mice, this role is shared with Hhip1.
